Viral Blips Were Infrequent in HIV-1-Infected Virologically-Suppressed Adults Treated with Tenofovir Alafenamide or Tenofovir DF Rilpivirine-Containing Regimens

Abstract

Background. Differences between regimens in the frequency of transient episodes of viremia (viral blips) as well as the impact of these viral blips on the risk of virologic failure and resistance development is not fully understood. Here we investigate the frequency of viral blips in virologically‐suppressed subjects switching to rilpivirine/ emtricitabine/tenofovir alafenamide (R/F/TAF) vs. maintaining R/F/tenofovir disoproxil fumarate (TDF) and the association of viral blips with clinical outcome through Week 48 of study GS‐US‐366‐1216. Methods. GS‐US‐366‐1216 is a randomized, double‐blind, phase 3b study evaluating the safety and efficacy of switching to R/F/TAF from R/F/TDF in HIV‐1‐infected virologically‐suppressed subjects. For the viral blip analysis, treated subjects with ≥1 post‐baseline HIV‐1 RNA value were included. All on‐drug HIV‐1 RNA data points and FDA snapshot outcome data through Week 48 were utilized. Plasma HIV‐1 RNA was measured using the Roche Taqman 2.0 assay. A viral blip was defined as any post‐baseline HIV‐1 RNA value ≥50 c/mL preceded and followed by HIV‐1 RNA <50 c/mL. Results. Of the 627 subjects included in the analysis, 23 (3.7%) experienced ≥1 blip through Week 48 and were distributed similarly between treatment groups (10/315, 3.2% R/F/TAF; 13/312, 4.2% R/F/TDF; P = 0.53; median 6 viral load measurements per subject). Twenty subjects had single blips (8 R/F/TAF, 12 R/F/TDF) and 3 subjects experienced 2 blips each (2 R/F/TAF, 1 R/F/TDF). Of 26 total blip events, 19 (73%) were lowlevel at 50‐199 c/mL. Among subjects with blips, 22/23 (96%) were virologic successes at Week 48 (9/10, 90% R/F/TAF; 13/13, 100% R/F/TDF), similar to those subjects without blips (568/604, 94% overall; 287/305, 94% R/F/TAF; 281/299, 94% R/F/TDF). One subject in the R/F/TAF group had 2 blips prior to experiencing virologic rebound with mutations also detected at baseline (determined by retrospective proviral DNA sequencing). Conclusion. Viral blips were infrequent among subjects switching to R/F/TAF or maintaining R/F/TDF through Week 48 of study GS‐US‐366‐1216. No differences in blip frequency or virologic failure post‐blip were observed between treatment groups. Most blips were low‐level (<200 c/mL) and most subjects with blips remained suppressed through Week 48.